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Background: Severe neonatal hyperbilirubinemia is associated with chronic bilirubin encephalopathy, or kernicterus, which is a rare disorder characterized by spasticity, hearing and vision abnormalities, and sometimes mental retardation. Reportedly occurring at a rate of 0.9 instances per 100,000 live births, kernicterus has a mortality rate of at least 10 percent and a morbidity rate of at least 70 percent. Severe hyperbilirubinemia has been used as a surrogate marker because no studies have directly measured kernicterus as an outcome. Screening, by risk factor and bilirubin measurement, and treatment of elevated bilirubin levels have become widespread to try to prevent kernicterus.

In 2007, the Center on Primary Care, Prevention and Clinical Partnerships at the Agency for Healthcare Research and Quality, on behalf of the U.S. Preventive Services Task Force (USPSTF), asked the Tufts Evidence-Based Practice Center to update its 2003 evidence report on hyperbilirubinemia. The USPSTF uses those findings in its screening recommendations for bilirubin encephalopathy in neonates. Trikalinos and colleagues summarized the key findings from the systematic review that examined the effects of screening for hyperbilirubinemia on the incidence of acute and chronic bilirubin encephalopathy.

The Study: The study addressed four key questions: (1) Does screening using risk-factor assessment and bilirubin testing reduce the incidence of acute or chronic bilirubin encephalopathy?; (2) Does risk-factor assessment correctly identify infants who may benefit from bilirubin testing?; (3) Does bilirubin testing correctly identify infants who may benefit from phototherapy?; and (4) What are the adverse effects of screening?

In the previous evidence report, investigators reviewed studies through August 2001; eligible studies for this review were identified by searching Medline for all English-language studies from September 2001 through August 2007 and included additional relevant articles obtained from the reference lists of the identified articles. Studies on healthy infants born at 35 weeks of gestation or later were eligible if they addressed screening by risk-factor scores, transcutaneous or serum bilirubin testing, or a combination of these. Each study was assigned a quality rating of good, fair, or poor based on USPSTF criteria and the presence or absence of flaws in the way the study was conducted. The identified studies were too dissimilar to allow a meta-analysis, so sensitivity and specificity pairs and positive and negative likelihood ratios were calculated for each study.

Results: Of the 742 abstracts and 96 articles reviewed, nine were eligible for the systematic review. None of the studies directly evaluated the effects of screening on bili-rubin encephalopathy, but used hyperbilirubinemia as a surrogate outcome. The four studies that reviewed two risk-assessment tools were considered to be of fair quality and showed comparable predictive ability to determine which infants would be at risk of significant hyperbilirubinemia. Studies of transcutaneous and serum bilirubin measurements were analyzed separately. Four studies reviewed early serum bilirubin testing; three were deemed fair and one poor for methodologic quality. All four showed comparable ability to predict postdischarge elevated bilirubin levels. The two studies on transcutaneous bilirubin measurement were of poor quality. None of the studies addressed the adverse effects of screening.

Screening by risk factors, bilirubin testing, or a combination is effective in predicting high bilirubin levels. In addition, noncontrolled studies suggest that early detection reduces the rate of readmission for hyperbilirubinemia. However, the literature assumes that high bilirubin levels are a valid marker for bilirubin encephalopathy, and that treating high bilirubin levels can prevent bilirubin encephalopathy. The small number of eligible studies, none of good methodologic quality, limited the ability to determine definitive answers to the study questions.

Conclusion: The authors conclude that high-quality evidence is lacking to determine the actual value of screening for hyperbilirubinemia to prevent chronic bilirubin encephalopathy.

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